|Bias||Author's judgement||Support for judgement|
|Quote: "Participants were randomly assigned in a 1:1:1:1:1 ratio through computer-generated blocks of various sizes and stratified by administrative region and severity of illness at enrolment... Randomization was implemented in the electronic Case Report Form to ensure appropriate allocation concealment".
Comment: Allocation sequence random. Allocation sequence concealed.
Imbalances in baseline characteristics appear to be compatible with chance. Chronic pulmonary diseases more common in the control arm (21%) than in the treatment arms (13%).
|Deviations from intervention||
Comment: Unblinded study.
No participant cross-over.
Administration of co-interventions of interest (antivirals, biologics, and corticosteroids) were reported and balanced between groups.
Data were analyzed using intention-to-treat analysis, which, to estimate the effect of assignment to intervention, was considered appropriate.
|Missing outcome data||
|Comment: 603 patients randomized; 583 patients analyzed for efficacy except viral negative conversion, 579 for safety.
Data available for >95% of population.
Risk assessed to be low for the outcomes: Mortality. Time to clinical improvement. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events.
For viral negative conversion, data were available for <95% of the population.
No evidence that the result is not biased.
Reasons for missing data unknown, hence no information on whether missingness could depend on its true value, but it is not considered likely to owing to the equal proportion of missingness.
Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion.
|Measurement of the outcome||
|Comment: Unblinded study
Mortality and viral negative conversion are observer-reported outcomes not involving judgement. For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment.
Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. WHO score 7 and above.
Clinical improvement (defined as improvement of 2 categories of the 7-point ordinal scale or hospital discharge) and WHO score 6 and above require clinical judgement and could be affected by knowledge of intervention receipt.
Also, the authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected outcomes. All these outcomes can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic.
Risk assessed to be some concerns for the outcomes: Time to clinical improvement. WHO score 6 and above. Adverse events. Serious adverse events.
|Selection of the reported results||
|Comment: The protocol, statistical analysis plan and trial registry were available.
Results were not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. Time to clinical improvement. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events.
|Overall risk of bias||